Characterization of artemisinin resistance in plasmodium falciparum
Artemisinins are an important class of antimalarials because of their remarkable antimalarial activity and exceptional safety profile. However, the decline in efficacy of artemisinin-based drugs jeopardizes global efforts that aim to control and ultimately eradicate malaria. In order to better under...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Theses and Dissertations |
| Language: | English |
| Published: |
2017
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/10356/72647 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | Artemisinins are an important class of antimalarials because of their remarkable antimalarial activity and exceptional safety profile. However, the decline in efficacy of artemisinin-based drugs jeopardizes global efforts that aim to control and ultimately eradicate malaria. In order to better understand the Artemisinin resistance phenotype, we developed Artemisinin-resistant parasite lines derived from two isogenic clones (6A and 11C) of the 3D7 strain of Plasmodium falciparum using a selection regimen that mimics how parasites interact with the drug in infected patients. Long term in vitro selection produced two parasite lines that displayed profound stage-specific resistance to artemisinin and its relative compounds. Chemosensitivity and transcriptional profiling of ART-resistant parasites indicate that enhanced adaptive responses against oxidative stress and protein damage are associated with the artemisinin resistance phenotype. Genomic characterization of both parasite lines also identified a spectrum of mutated and copy number-variable genes that could play a role in mediating artemisinin sensitivity. Collectively, this work represents a useful resource for investigating artemisinin response and resistance in P. falciparum. |
|---|